The DNA at the ends of the telomeres of chromosomes in mammalian cells consists of double- and single-stranded nucleic acid composed of many tandem repeats of a simple nucleotide sequence referred to as the telomeric repeat sequence. Telomeres help maintain chromosome structure and function; the loss of telomeric DNA can activate the cellular processes that detect and control DNA damage and monitor and control cell proliferation and senescence. The maintenance of telomeres and the regulation of telomere length are vital cellular functions involved in transmitting genetic information from generation to generation, aging, the control of cell growth, and cancer. See Harley, 1991, Mutation Research 256:271-282; and Blackburn, 1992, Annu. Rev. Biocheni. 61:113-129, each of which is incorporated herein by reference (note: references cited herein are provided for convenience; such citations are not to be construed as an admission of prior invention).
The multi-component telomerase ribonucleoprotein enzyme catalyzes the synthesis of the first strand of telomeric DNA synthesized during telomere elongation, using the RNA component of the enzyme as a template. Although the RNA component of human telomerase (hTR) and other mammalian telomerase enzymes has been identified, isolated, characterized, and described in the scientific literature, the protein components of the telomerase enzyme as well as most other cellular macromolecules involved in telomere maintenance and the regulation of telomere length and telomerase activity in mammalian cells have not. See Feng et al., 1995, Science 269:1236-1241; PCT patent publication No. 96/01835; and pending U.S. patent application Ser. No. 08/521,634, filed Aug. 31, 1995, and Ser. No. 08/330,123, filed Oct. 27, 1994, each of which is incorporated herein by reference.
Many useful methods and reagents relating to telomere and telomerase biology have been described. See, e.g., U.S. Pat. No. 5,489,508; PCT patent publication Nos. 95/23572, 95/13381, 95/13382, and 95/13383; and U.S. patent application Ser. No. 08/632,662, filed Apr. 15, 1996, each of which is incorporated herein by reference. Significant improvements to and new opportunities for telomere- and telomerase-mediated therapies as well as related assays, screens, diagnostic methods, and reagents could be realized and obtained, however, if additional cellular macromolecules involved in mammalian telomere maintenance and the regulation of telomere length and telomerase activity could be identified, characterized, and made available in pure or isolatable form. In particular, the characterization of the nucleotide and corresponding amino acid sequences of such macromolecules could provide new and useful recombinant expression vectors and plasmids, as well as related reagents useful in medical therapeutic and diagnostic technology.